Longitudinal association of oral functions and dementia in Japanese older adults

The relationship between oral functions and dementia was examined in 7384 older adults (age ≥ 75 years) who visited a dental clinic in Gifu, Japan. Participants without dementia in a baseline survey in April 2018 were followed until March 2021. As oral functions, chewing function, tongue and lip function, and swallowing function were assessed by self-administered questionnaire, by oral diadochokinesis test, and by repetitive saliva swallowing test, respectively. The presence of systemic diseases was based on data obtained from the National Database of Health Insurance of Japan. At follow-up, 415 (6%) participants were diagnosed with dementia. Multivariate logistic regression analyses showed the presence of dementia at follow-up was associated with female (odds ratio [OR] 1.386; 95% confidence interval [CI] 1.117–1.719), age (OR 1.078; CI 1.056–1.101), regular dental checkups (absence; OR 1.452; CI 1.180–1.788), brushing frequency ≥ twice/day (absence; OR 1.510; CI 1.194–1.911), decayed teeth (presence; OR 1.328; CI 1.071–1.648), swallowing function (poor; OR 1.484; CI 1.135–1.939) at baseline. It was found that poor swallowing function was associated with the future onset of dementia.


Survey items in the National Health Insurance database system
The information about sex, age, and presence or absence of hypertension, diabetes mellitus, and dementia was obtained from the National Database of Health Insurance of Japan (NDB) 15 .Presence or absence with dementia was investigated both at baseline and follow-up, and Participants with dementia at follow-up selected as outcome.

Smoking habits and oral items
Data on the following smoking habits and oral items were obtained at baseline: presence or absence of regular dental checkups, presence or absence of brushing frequency ≥ twice/day, presence or absence of number of present teeth ≥ 20, presence or absence of decayed teeth, presence or absence of periodontal pockets ≥ 4 mm, chewing function, tongue and lip function, and swallowing function.The data for the oral items were provided by the Gifu Dental Association, Japan.For smoking habits, participants who smoked at least one cigarette per day were included (presence or absence) 15,16 .Regular dental checkups were considered to involve regular visits to the dental clinic (at least once every 6 months or less than once every 6 months) 15,17 .The number of decayed teeth was calculated as D (Decayed), missing teeth as M (Missing), and filled teeth as F (Filled), and the number of DMF teeth was used to evaluate dental caries history 15,18 .The coded values of the Community Periodontal Index (CPI) were used to evaluate periodontal pockets ≥ 4 mm, with codes 1 and 2 being evaluated as periodontal pockets ≥ 4 mm 15,19 .Chewing function was assessed by difficulty eating hard food.Participants were asked to choose from "It is more difficult to eat hard food than it was six months ago (presence or absence)" in the selfadministered questionnaire 15,20 .Tongue and lip function was assessed using the oral diadochokinesis test for tongue and lip function, with poor tongue and lip function defined as less than 30 syllables in 5 s of any one of "Pa", "Ta", or "Ka" 15,21 .For swallowing function, those who swallowed less than 3 times in 30 s in the repetitive saliva swallowing test were evaluated as having poor swallowing function 15,22 .

Statistical analysis
The Kolmogorov-Smirnov test was used to check the normality of the data.Because all continuous variables were not normally distributed, data are expressed as medians (first and third quartiles).The chi-squared test was used to evaluate significant differences in characteristics of oral functions with and without dementia.Univariate and multivariate logistic regression analyses were performed with presence of dementia as the dependent variable.In the multivariate stepwise logistic regression analysis, variables with p > 0.10 were excluded from the model 23 .Additionally, variables that were significantly different in univariate logistic regression analysis were selected into a third category in addition to gender and age.A Hosmer-Lemeshow fit test was performed to confirm the goodness of fit of our model.A statistical analysis software (SPSS statistics version 27; IBM Japan, Tokyo, Japan) was used to analyze all data.A p values < 0.05 were considered significant 15 .

Research ethics
Our study is an experiment involving human participants and informed consent has been obtained in writing from all participants and/or their legal guardians, and the confirmation document is attached separately (Fig. 2).Our study was approved by the Ethics Committee of Asahi University (No. 33006) and was performed in accordance with the Declaration of Helsinki (as revised in Brazil 2013).

Results
Table 1 shows the characteristics of the participants at baseline and at follow-up.Overall, there were 3078 males (42%) and 4306 females (58%).The proportion of participants with hypertension (p < 0.001) was significantly higher at follow-up than at baseline.In addition, the proportion of participants with number of present teeth ≥ 20 (p < 0.001) was significantly lower at follow-up than at baseline.However, there were no significant differences in the other factors, except the proportions of those with hypertension and with number of present teeth ≥ 20, between at baseline and at follow-up.
Table 2 shows the characteristics of oral functions at baseline by with and without dementia at follow-up.In the present study, 415 participants (6%) were newly diagnosed with dementia at follow-up.Participants with dementia were characterized by a significantly higher proportion of poor tongue and lip function (p = 0.028) and poor swallowing function (p < 0.001) than those without dementia.On the other hand, there was no significant association between chewing function and dementia.
Table 4 shows adjusted OR and 95% CI for dementia at follow-up.After adjusting for after adjusted for gender, age, hypertension, regular dental checkups, brushing frequency ≥ twice/day, number of present teeth ≥ 20, decayed

Discussion
To the best of our knowledge, this is the first longitudinal study to examine the associations between swallowing function and dementia in Japanese older adults using data from the NDB.The results showed that participants with dementia after two years of follow-up had a higher proportion of poor swallowing function at baseline than those without dementia.The results of logistic regression analysis showed that, after adjusting for gender, age, hypertension, regular dental checkups, brushing frequency ≥ twice/day, number of present teeth ≥ 20, decayed teeth, and tongue and lip function, the presence or absence of dementia after 2 years was associated with swallowing function at baseline.From these results, it was predicted that a decrease in swallowing function was associated with a higher risk of the onset of dementia in the future.There are several possible mechanisms for the relationship between swallowing function and dementia.Swallowing actions activate brain function and improve learning and memory skills 24,25 .It was also reported that swallowing actions increase cerebral blood flow and the partial pressure of oxygen in the brain 26 .Decreased cerebral blood flow is a known risk factor for dementia 27 .Thus, participants with swallowing difficulties might www.nature.com/scientificreports/have a greater risk for dementia because of reduced cerebral blood flow and even ischemia.In addition, people with poor swallowing function tend to consume less fruit and vegetables and more high-energy foods than those with good swallowing function 28 .High-calorie diets rich in carbohydrates and saturated fatty acids tend to increase the risk of dementia 29 .Therefore, these may be also among the mechanisms.However, further research is needed to clarify the mechanisms by which poor swallowing function is associated with dementia.
In the present study, chewing function was not associated with dementia.A previous report showed an association between chewing function using the evaluation of chewing function was based on muscle activity of the masticatory muscles and dementia 30 .The results in the previous and present studies may have been different due to their different methods.In the future, we would like to consider judging chewing function by methods such as assessing the distribution of crushed particles in chewing samples (e.g., gummy jellies), the amount of elution of contents in chewing samples, or the activity of the masticatory muscles.
In addition, a cross-sectional study reported an association between poor tongue and lip function and dementia using the same research methodology as the present study 31 .This finding differs from the present study.This may be related to differences in research methods (cross-sectional vs. longitudinal studies).It may also be related to the bias in the proportion of participants with poor tongue and lip function at baseline.In the previous study, most participants possessed good tongue and lip function 31 , the present study.Therefore, external validity should be considered in this study.
In the present study, lack of regular dental checkups and decayed teeth were associated with dementia.Past reports showed that recommendations for regular dental checkups reduced the risk of dementia onset 32 .Furthermore, it was reported that mutans bacteria that cause tooth decay adhere to the walls of blood vessels in the brain and reduce cognitive function 33 .These previous studies support the results of the present study.These studies reported that maintaining a good oral environment and controlling oral bacteria decrease the risk of dementia onset.In the present study, brushing frequency ≥ twice/day was associated with dementia.It is widely known that proper brushing habits are important for preventing decayed teeth and maintaining a good oral environment 34,35 .Therefore, participants in the present study who brushed ≥ twice/day may have engaged in proper brushing habits, had a good oral environment, and may not have had decayed teeth, and thus had a lower risk of dementia onset.Therefore, brushing habits may indirectly contribute to delaying the onset of dementia via maintaining a good oral environment.
There was no association between number of present teeth and dementia in our study.Past studies were reported that missing tooth is associated with development of Alzheimer's dementia 36 .This may be related to number of participants with missing tooth.In our study, proportion of participants with number of present teeth ≥ 20 was 66%, which is very higher than average in older adults aged ≥ 75 years in Japan (51.6%) 37 .Therefore, it is possible that there was no association between number of present teeth and dementia because number of participants with missing tooth was too small.
A major strength of the present study is its sample size of more than 7000 Japanese older adults.In addition, it was a longitudinal study, which is useful for establishing a causal relationship between dementia and poor swallowing function and for inferring factors that contribute to pressure on social security costs in Japan.Furthermore, it was possible to gather study population data from multiple locations in Gifu, Japan (Gifu City, Kagamihara City, Kani City, and Ogaki City).
In the present study, the Hosmer-Lemeshow fit test was used in a multivariate logistic regression analysis model.The Hosmer-Lemeshow fit test is used to examine the fit of a multivariate logistic regression analysis model and tests whether the observed event rate in a subgroup model fits the expected event rate.The Hosmer-Lemeshow test is considered to show a good fit with p values > 0.05 38 .In the present study, the p value was 0.288, suggesting a good fit.
However, there are several limitations to the present study.First, since participants of the present study visited to dental checkups, they may have been a highly health-conscious population.In our study, 8.6% of all participants were certified as needing supports and 6.9% were certified as needing cares based on Long-Term Care Insurance Law in Japan at baseline.This was a low value compared to proportion with certified as needed supports (8.8%) and needed cares (23.1%) in older adults aged ≥ 75 years in Japan 2 .Second, the presence or absence of diseases not in the database is unknown, since the NDB was used.Finally, our study is a longitudinal study,

Figure 1 .
Figure 1.Flowchart of data selection criteria.

Figure 2 .
Figure 2. The confirmation document form used to obtain informed consent.

Table 2 .
Baseline characteristics regarding oral functions of the study participants with and without dementia at follow-up.*p < 0.05, using Fishers exact test.

Table 3 .
Crude OR and 95% CI for dementia at follow-up.OR odds ratio, CI confidence interval.

Table 4 .
Adjusted OR and 95% CI for dementia at follow-up.Adjustment for gender, age, hypertension, regular dental checkups, brushing frequency ≥ twice/day, number of present teeth ≥ 20, decayed teeth, tongue and lip function, and swallowing function.OR odds ratio, CI confidence interval.